Measuring the Metabolic Evolution of Glioblastoma throughout Tumor Development, Regression, and Recurrence with Hyperpolarized Magnetic Resonance

Salzillo, Travis C.; Mawoneke, Vimbai; Weygand, Joseph; Shetty, Anil; Gumin, Joy; Zacharias, Niki M.; Gammon, Seth T.; Piwnica‐Worms, David; Fuller, Gregory N.; Logothetis, Christopher J.; Lang, Frederick F.; Bhattacharya, Pratip K.

doi:10.3390/cells10102621

Cited by 6 publications

(8 citation statements)

References 94 publications

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“…MRL adaptation has traditionally been employed for the management of interfractional tumoral and OAR changes in shape and position. However, MRI has also been used for assessing biological and physiological information [ 179 , 180 , 181 ], as well as for MRI techniques termed mpMRI [ 182 ]. One such technique is diffusion-weighted imaging [ 183 ] which enabled the detection of changes in water mobility [ 184 ].…”

Section: Future Directionsmentioning

confidence: 99%

Stereotactic Magnetic Resonance-Guided Adaptive and Non-Adaptive Radiotherapy on Combination MR-Linear Accelerators: Current Practice and Future Directions

Bryant

Weygand

Keit

et al. 2023

Cancers

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Stereotactic body radiotherapy (SBRT) is an effective radiation therapy technique that has allowed for shorter treatment courses, as compared to conventionally dosed radiation therapy. As its name implies, SBRT relies on daily image guidance to ensure that each fraction targets a tumor, instead of healthy tissue. Magnetic resonance imaging (MRI) offers improved soft-tissue visualization, allowing for better tumor and normal tissue delineation. MR-guided RT (MRgRT) has traditionally been defined by the use of offline MRI to aid in defining the RT volumes during the initial planning stages in order to ensure accurate tumor targeting while sparing critical normal tissues. However, the ViewRay MRIdian and Elekta Unity have improved upon and revolutionized the MRgRT by creating a combined MRI and linear accelerator (MRL), allowing MRgRT to incorporate online MRI in RT. MRL-based MR-guided SBRT (MRgSBRT) represents a novel solution to deliver higher doses to larger volumes of gross disease, regardless of the proximity of at-risk organs due to the (1) superior soft-tissue visualization for patient positioning, (2) real-time continuous intrafraction assessment of internal structures, and (3) daily online adaptive replanning. Stereotactic MR-guided adaptive radiation therapy (SMART) has enabled the safe delivery of ablative doses to tumors adjacent to radiosensitive tissues throughout the body. Although it is still a relatively new RT technique, SMART has demonstrated significant opportunities to improve disease control and reduce toxicity. In this review, we included the current clinical applications and the active prospective trials related to SMART. We highlighted the most impactful clinical studies at various tumor sites. In addition, we explored how MRL-based multiparametric MRI could potentially synergize with SMART to significantly change the current treatment paradigm and to improve personalized cancer care.

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Section: Future Directionsmentioning

confidence: 99%

Stereotactic Magnetic Resonance-Guided Adaptive and Non-Adaptive Radiotherapy on Combination MR-Linear Accelerators: Current Practice and Future Directions

Bryant

Weygand

Keit

et al. 2023

Cancers

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“…Another area of clinical brain cancer imaging where the application of HP [1- 13 C] pyruvate can make an impact in determination of pseudo-progression (an increase in tumor size might be due to infiltration of immune cells and accumulation of fluids, followed by a regression of tumor size) following different brain cancer therapies. This has been successfully shown in preclinical models with hyperpolarized metabolic imaging after radiation [ 25 ].…”

Section: Brain Cancermentioning

confidence: 99%

Enhancing Cancer Diagnosis with Real-Time Feedback: Tumor Metabolism through Hyperpolarized 1-13C Pyruvate MRSI

et al. 2023

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This review article discusses the potential of hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging (MRSI) as a noninvasive technique for identifying altered metabolism in various cancer types. Hyperpolarization significantly improves the signal-to-noise ratio for the identification of 13C-labeled metabolites, enabling dynamic and real-time imaging of the conversion of [1-13C] pyruvate to [1-13C] lactate and/or [1-13C] alanine. The technique has shown promise in identifying upregulated glycolysis in most cancers, as compared to normal cells, and detecting successful treatment responses at an earlier stage than multiparametric MRI in breast and prostate cancer patients. The review provides a concise overview of the applications of HP [1-13C] pyruvate MRSI in various cancer systems, highlighting its potential for use in preclinical and clinical investigations, precision medicine, and long-term studies of therapeutic response. The article also discusses emerging frontiers in the field, such as combining multiple metabolic imaging techniques with HP MRSI for a more comprehensive view of cancer metabolism, and leveraging artificial intelligence to develop real-time, actionable biomarkers for early detection, assessing aggressiveness, and interrogating the early efficacy of therapies.

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“…All 13 C spectra were acquired using a single-pulse, fast, low-angle shot sequence with a flip angle of 20 • , image size of 2048 × 90, single slice with a thickness of 8-12 mm, and repetition time of 2 s over a period of 180 s to detect [1- 13 C] pyruvate and its metabolic product lactate. A 13 C-urea phantom was used as a spectroscopic reference and tumor location reference [48]. All imaging procedures were performed in accordance with regulations of the MD Anderson Institutional Animal Care and Use Committee.…”

Section: Magnetic Resonance Imaging and Hyperpolarized Mr Data Acquis...mentioning

confidence: 99%

Identifying the Metabolic Signatures of PPARD-Overexpressing Gastric Tumors

Pudakalakatti

Titus

Enriquez

et al. 2022

IJMS

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Peroxisome proliferator-activated receptor delta (PPARD) is a nuclear receptor known to play an essential role in regulation of cell metabolism, cell proliferation, inflammation, and tumorigenesis in normal and cancer cells. Recently, we found that a newly generated villin-PPARD mouse model, in which PPARD is overexpressed in villin-positive gastric progenitor cells, demonstrated spontaneous development of large, invasive gastric tumors as the mice aged. However, the role of PPARD in regulation of downstream metabolism in normal gastric and tumor cells is elusive. The aim of the present study was to find PPARD-regulated downstream metabolic changes and to determine the potential significance of those changes to gastric tumorigenesis in mice. Hyperpolarized [1-13C] pyruvate magnetic resonance spectroscopy, nuclear magnetic resonance spectroscopy, and liquid chromatography-mass spectrometry were employed for metabolic profiling to determine the PPARD-regulated metabolite changes in PPARD mice at different ages during the development of gastric cancer, and the changes were compared to corresponding wild-type mice. Nuclear magnetic resonance spectroscopy-based metabolomic screening results showed higher levels of inosine monophosphate (p = 0.0054), uracil (p = 0.0205), phenylalanine (p = 0.017), glycine (p = 0.014), and isocitrate (p = 0.029) and lower levels of inosine (p = 0.0188) in 55-week-old PPARD mice than in 55-week-old wild-type mice. As the PPARD mice aged from 10 weeks to 35 weeks and 55 weeks, we observed significant changes in levels of the metabolites inosine monophosphate (p = 0.0054), adenosine monophosphate (p = 0.009), UDP-glucose (p = 0.0006), and oxypurinol (p = 0.039). Hyperpolarized [1-13C] pyruvate magnetic resonance spectroscopy performed to measure lactate flux in live 10-week-old PPARD mice with no gastric tumors and 35-week-old PPARD mice with gastric tumors did not reveal a significant difference in the ratio of lactate to total pyruvate plus lactate, indicating that this PPARD-induced spontaneous gastric tumor development does not require glycolysis as the main source of fuel for tumorigenesis. Liquid chromatography-mass spectrometry-based measurement of fatty acid levels showed lower linoleic acid, palmitic acid, oleic acid, and steric acid levels in 55-week-old PPARD mice than in 10-week-old PPARD mice, supporting fatty acid oxidation as a bioenergy source for PPARD-expressing gastric tumors.

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Measuring the Metabolic Evolution of Glioblastoma throughout Tumor Development, Regression, and Recurrence with Hyperpolarized Magnetic Resonance

Cited by 6 publications

References 94 publications

Stereotactic Magnetic Resonance-Guided Adaptive and Non-Adaptive Radiotherapy on Combination MR-Linear Accelerators: Current Practice and Future Directions

Stereotactic Magnetic Resonance-Guided Adaptive and Non-Adaptive Radiotherapy on Combination MR-Linear Accelerators: Current Practice and Future Directions

Enhancing Cancer Diagnosis with Real-Time Feedback: Tumor Metabolism through Hyperpolarized 1-13C Pyruvate MRSI

Identifying the Metabolic Signatures of PPARD-Overexpressing Gastric Tumors

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